Effects of angiotensin-II receptor blockers on experimental autoimmune myocarditis

Background: The effects of angiotensin-II type 1 receptor blockers (ARBs) on the treatment of hypertension, heart failure, and other cardiovascular diseases have been confirmed extensively. However, recent studies have emphasized the nonhemodynamic effects of these drugs. The purpose of this study was to investigate the effects of ARBs on the development of experimental autoimmune myocarditis (EAM), and to clarify the mechanisms involved. Methods: EAM model was induced in Lewis rats by injection of porcine cardiac myosin subcutaneously. We administered valsartan (a new ARB) to rats with EAM and measured blood pressure regularly. Echocardiography was performed to examine the cardiac function and heart structure of the rats. The severity of myocarditis was detected by histopathological evaluation. We evaluated antigen-specific T-cell proliferation responses to cardiac myosin by the lymphocyte proliferation assay and measured serum levels of Th1 and Th2 cytokines by enzyme-linked immunosorbent assay. Results: There was no significant difference in the blood pressure (BP) level between the groups and cardiac function of valsartan-treated rats was significantly improved compared with untreated rats. Valsartan markedly reduced the severity of myocardial lesions and suppressed lymphocyte proliferation in rats immunized with myosin. After drug administration, Th1 cytokines (IFN-gamma and IL-2) were significantly down-regulated, while Th2 cytokines (IL-4 and IL-10) were detected to undergo up-regulation. Conclusions: The results suggest that valsartan can ameliorate EAM independent of BP-lowering effects. Some of the beneficial effects of ARBs may be due to their immunomodulatory reactions in the modification of helper T-cell balance. (C) 2009 Elsevier Ireland Ltd. All rights reserved.